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GSE49314
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The maintenance of the TFH phenotype depends on continuous signals via ICOS. For a global assessment of differences in gene expression after interruption of the ICOS pathway a genome wide transcriptome analysis was performed. We used the OT-II adoptive transfer system to isolate antigen-specific TFH cells (day 6 after immunization) after short-term (6 hours) blockade of the ICOS pathway using a monoclonal antibody against ICOS-L.
Publication Title
ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
There is some emerging evidence that members of the Schlafen (SLFN) family of proteins mediate antineoplastic responses, but the mechanisms accounting for these effects are not known. We provide evidence that human SLFN5, an interferon (IFN)- inducible member of the family, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of matrix metalloproteinases (MMP)-1 and -13 and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression. Overall design: Examination of 2 SLFN5 knockdown cells and 2 controls, in triplicate.
Publication Title
Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
The Caenorhabditis elegans somatic gonad was the first organ to have its cell lineage determined, and the gonadal lineages of the two sexes differ greatly in their pattern of cell divisions, cell migration and cell types. Despite much study, the genetic pathways that direct early gonadal development and establish its sexual dimorphism remain largely unknown, with just a handful of regulatory genes identified from genetic screens. To help define the genetic networks that regulate gonadal development, we employed cell-specific RNA-seq. We identified transcripts present in Z1/Z4 or Z1/Z4 daughter cells in each sex at the onset of somatic gonadal sexual differentiation. For comparison, transcripts were identified in whole animals at both time points. Pairwise comparisons of samples identified several hundred gonad-enriched transcripts, including most known Z1/Z4-enriched mRNAs, and reporter analysis confirmed the effectiveness of this approach. Prior to the Z1/Z4 division few sex-biased Z1/Z4 transcripts were detectable, but less than six hours later, we identified more than 250 sex-biased transcripts in the Z1/Z4 daughters, of which about a third were enriched in the somatic gonad cells compared to cells from whole animals. This indicates that a robust sex-biased developmental program, some of it gonad-specific, initiates in these cells around the time of the first Z1/Z4 division. Cell-specific analysis also identified approximately 70 previously unannotated mRNA isoforms that are enriched in Z1/Z4 or their daughters. Our data suggest that early sex differentiation in the gonad is controlled by a relatively small suite of differentially expressed genes, even after dimorphism has become apparent. Overall design: 20 total sample: two time points, two sexes, and gonadal cells or whole animals. The earlier time point was collected in triplicate and was harvested 9.5 hours after starved, hatched L1s were fed. The later time point was collected in duplicate and was harvested 15 hour after starved, hatched L1 were fed. Replicates of either dissociated whole animals or gonadal cells (Z1/Z4 or Z1/Z4 daughter) from both male and hermaphrodites were harvested for each time point.
Publication Title
Cell-Specific mRNA Profiling of the Caenorhabditis elegans Somatic Gonadal Precursor Cells Identifies Suites of Sex-Biased and Gonad-Enriched Transcripts.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Post-hybridization washing is an essential part of microarray experiments. Both, the quality of the experimental washing protocol and the adequate consideration of washing in intensity calibration ultimately affect the quality of the expression estimates extracted from the microarray intensities. We conducted experiments on GeneChip microarrays with altered protocols for washing, scanning and staining to study the probe-level intensity changes as a function of washing cycles. Particularly, three Affymetrix GeneChip HGU133plus2 arrays were hybridized and equilibrated for 16 hours in the hybridization oven. For one of the three arrays washing and staining was performed according to the manufacturers instructions. For another array the first scan was done immediately after low stringent wash and staining without intermitting stringent washing. Then, the array was stringently washed and scanned in alternating order three more times where each washing step consists of a definite number of washing cycles. The third array was low stringently washed followed by two stringent washing cycles and staining before the first scan. Subsequently it was analogously processed as array A. All three chips are repeatedly processed in a second series of alternating wash/scan-cycles which was performed using the same protocol for each chip as in the first series as described above. As in the first series the arrays were also stained a second time to compensate for any loss of bleached fluorescent dye. Analysis of the washing kinetics shows that the signal-to-noise ratio doubles roughly every ten stringent washing cycles. Washing can be characterized by time-dependent rate constants which reflect the heterogeneous character of target binding to microarray probes. We propose an empirical washing function which estimates the survival of probe bound targets. The washing function allows calibrating probe intensities for the effect of washing. On a relative scale, proper calibration for washing markedly increases expression measures especially in the limit of small and large values.
Publication Title
Washing scaling of GeneChip microarray expression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 139 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements.
Publication Title
MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Geminin is a small nucleoprotein that neuralizes ectoderm in the Xenopus embryo. Geminin promotes neural fate acquisition of mouse embryonic stem cells: Geminin knockdown during neural fate acquisition decreased expression of neural precursor cell markers (Pax6, Sox1), while increasing expression of Pitx2, Lefty1 and Cited2, genes involved in formation of the mouse node. Here we differentiated mouse embryonic stem cells into embryoid bodies to study Geminin's ability to repress primitive streak mesendoderm fate acquisition. We used microarrays to define the sets of genes that are regulated by Geminin during cell fate acquisition in embryoid bodies, using Dox-inducible Geminin knockdown or overexpression mouse embryonic stem cell lines.
Publication Title
Geminin restrains mesendodermal fate acquisition of embryonic stem cells and is associated with antagonism of Wnt signaling and enhanced polycomb-mediated repression.
Sample Metadata Fields
Specimen part
View Samples- Xenopus laevis
- 12 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo: Transient maintenance of a pluripotent embryonic cell population followed by the onset of multi-lineage commitment is a fundamental aspect of development. However, molecular regulation of this transition is not well characterized in vivo. Here we demonstrate that the nuclear protein Geminin is required to restrain commitment and spatially restrict mesoderm, endoderm, and non-neural ectoderm to their proper locations in the Xenopus embryo. We used microarray analyses to demonstrate that Geminin overexpression represses many genes associated with cell commitment and differentiation, while elevating expression levels of genes that maintain pluripotent early and immature neurectodermal cell states. We characterized Geminins relationship to cell signaling and found that Geminin broadly represses Activin-, FGF-, and BMP-mediated cell commitment. Conversely, Geminin knockdown enhances commitment responses to growth factor signaling and causes ectopic mesodermal, endodermal, and epidermal fate commitment in the embryo. We also characterized Geminins functional relationship with transcription factors that had similar activities and found that Geminin represses commitment independent of Oct4 ortholog (Oct25/60) activities, but depends upon intact Polycomb repressor function. Consistent with this, chromatin immunoprecipitation assays directed at mesodermal genes demonstrate that Geminin promotes Polycomb binding and Polycomb-mediated repressive histone modifications, while inhibiting modifications associated with gene activation. This work defines Geminin as an essential regulator of the embryonic transition from pluripotency through early multi-lineage commitment, and demonstrates that functional cooperativity between Geminin and Polycomb contributes to this process.
Publication Title
Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Nematode derived substances are known to down regulate host immune responses in order to survive in the human host. Brugia malayi is a parasitic nematode responsible for long lasting and disabling infection known as lymphatic filariasis in humans. The therapeutic benefit of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) has been demonstrated in both animal and human models. However the inability of individual purified nematode proteins to recreate this beneficial effect has limited the application of component immunotherapy to human disease. This experiment addresses the hypothesis that the genes regulated by IL8 and recombinant Brugia malayi AsnRS (rBmAsnRS) are different even though it is known that both molecules interact with IL-8 receptors. Furthermore, we theorize that the signal transduction pathways activated by IL-8 and rBmAsnRS are different because it is known that the extracellular G protein loops utilized by IL-8 and rBmAsnRS to activate IL8 receptors, are different. These results obtained with a single recombinant nematode protein, rBmAsnRS, share immunological features with those observed in a whole nematode infection and include desirable features for treatment of idiopathic inflammatory diseases, such as IBD.
Publication Title
Nematode asparaginyl-tRNA synthetase resolves intestinal inflammation in mice with T-cell transfer colitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate. Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined. Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, in neural fate acquisition from mouse embryonic stem (ES) cells. While Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate. Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses. These data demonstrate that Geminins activity contributes to mammalian neural cell fate acquisition. We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes. Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro. These findings define a novel activity for Geminin in regulation of chromatin structure. Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation.
Publication Title
Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 26 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This work uses a time series in order to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to NO3- provision. The experimental approach has been to monitor genome response to NO3- at 3, 6, 9, 12, 15 and 20 min, using ATH1 chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by very fast (within 3 min) gene expression modulation, involving genes/functions needed to prepare plants to use/reduce NO3-. State-space modeling (a machine learning approach) has been used to successfully predict gene behavior in unlearnt conditions.
Publication Title
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate.
Sample Metadata Fields
Specimen part, Treatment
View Samples